Can focal therapy successfully control prostate cancer? Also, if so, which patients should be considered eligible? With limited data available from relatively few patients, these questions are difficult to answer. At this writing, the most likely candidates for focal therapy are patients with low-risk, small-volume tumors, located in 1 region or sector of the prostate, who would benefit from early intervention. The difficulty lies in reliably identifying these men. The larger number of cores obtained in each needle biopsy session has increased both the detection of prostate cancer and the potential risk of overtreating many patients whose cancers pose very little risk to life or health. Urologists typically perform at least a 12-core template biopsy. Although the debate continues about the optimal template, laterally and peripherally directed biopsies have been shown to improve the diagnostic yield. However, as many as 25% of tumors arise anteriorly and can be missed with peripherally directed techniques. Prostate cancer tends to be multifocal, even in its earliest stages. However, the secondary cancers are usually smaller and less aggressive than the index cancer. They appear similar to the incidental cancers found in cystoprostatectomy specimens and appear to have little effect on prognosis in surgical series. When a single focus of cancer is found in 1 core, physicians rightly suspect that more foci of cancer are present in the prostate. Assessing the risk in these patients is challenging when determined by the biopsy data alone. To predict the presence of a very low-risk or "indolent" cancer, nomograms have been developed to incorporate clinical stage, Gleason grade, prostate-specific antigen levels, and prostate volume, along with the quantitative analysis of the biopsy results. Transperineal "mapping" or "saturation" biopsies have been advocated to detect cancers missed or underestimated by previous transrectal biopsies. This approach could provide the accurate staging, grading, and tumor localization needed for a focal therapy program. Nevertheless, for men with minimal cancer who are amenable to active surveillance or focal therapy, consensus about the most accurate biopsy strategy has not yet been reached. Imaging, particularly magnetic resonance imaging and magnetic resonance spectroscopic imaging, has been used to assess men with early-stage prostate cancer. Large-volume cancers can be seen reasonably well, but small lesions have been difficult to detect reliably or measure accurately. Factors such as voxel resolution, organ movement, biopsy artifact, and benign changes have limited the consistent estimation of the quantitative tumor volume. Nevertheless, magnetic resonance imaging and magnetic resonance spectroscopic imaging can aid in evaluating patients with prostate cancer being considered for focal therapy by providing additional evidence that the patient does not harbor an otherwise undetected high-risk, aggressive cancer. In some cases, imaging can usefully identify the location of even a limited-sized index cancer. When imaging findings are substantiated by mapping biopsy results, confidence in the accurate characterization of the cancer is enhanced. Correlating the imaging results with tissue changes during and after treatment can be of use in monitoring the ablative effects in the prostate and in assessing for tumor recurrence. More work is necessary before staging studies can uniformly characterize a prostate cancer before therapy, much less reliably identify and locate small-volume cancer within the prostate. However, exploring the role of focal ablation as a therapeutic option for selected men with low-risk, clinically localized, prostate cancer need not await the emergence of perfectly accurate staging studies, any more than the application of radical surgery or radiotherapy have. Modern biopsy strategies, combined with optimal imaging and nomograms to estimate the pathologic stage and risk, taken together, provide a sound basis for the selection of appropriate patients for entry into prospective clinical trials of focal therapy.